Interactions of cell penetrating peptide Tat with model membranes: A biophysical study

The protein transduction domain of the HIV-1 transactivator of transcription, Tat (Tat((48-60))), has been shown to transport P10, a cytotoxic peptide mimic of the cyclin dependent kinase inhibitor p(21WAF1/CIP1), into the nucleus of cancerous cells and induce apoptosis. Here, monolayer studies were used to investigate the membrane interactions of Tat((48-60)), P10 and the construct Tat((48-60))P10. It was found that Tat((48-60)) showed no significant surface activity but that both P10 and Tat((48-60))P10, were highly surface active, inducing surface pressure changes of 9.7 and 8.9 mN m(-1), respectively, with DMPS monolayers. The comparison of Tat((48-60))P10 and P10 surface interactions would be consistent with a hypothesis that the cargo attachment influences the capacity of the Tat-protein transduction domain to mediate transport across membranes either directly or via localisation of the construct at the membrane interface. (C) 2007 Elsevier Inc. All rights reserved.